A role for Elongin in Mediator recruitment at ATF6a regulated genes [Cut&Tag]

The bZIP transcription factor ATF6a is a master regulator of endoplasmic reticulum (ER) stress response genes. In this report, we identify the multifunctional RNA polymerase II transcription factor Elongin as a cofactor for ATF6a-dependent transcription activation. Biochemical studies reveal that Elongin functions at least in part by facilitating ATF6a-dependent loading of Mediator at the promoters and enhancers of ER stress response genes. Depletion of Elongin from cells leads to impaired transcription of ER stress response genes and to defects in the recruitment of Mediator and, in particular, its CDK8 kinase subunit. Taken together, these findings bring to light a new role for Elongin as a loading factor for Mediator during the ER stress response. Overall design: Cut&Tag in HCT116 cells with siRNA targeting Elongin A (siELOA) or control non-targeting siRNA (nonT), followed by induction of ER stress with 300 nM thapsigargin (Tg).